Tamibarotene

Summary

Tamibarotene (CHEMBL25202) is an approved small-molecule antineoplastic agent targeting RARA, RARB, and RARG; indicated across 10 conditions including myelodysplastic syndrome and crohn disease; with CIViC clinical evidence for 1 variant-indication association (e.g. PML K227_T233del in acute promyelocytic leukemia).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 3 (RARA, RARB, RARG)
• Indications: 10 conditions
• Clinical trials: 12
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 351.4 Da · C22H25NO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL25202
Name	Tamibarotene
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	108143
ChEBI	CHEBI:32181
Molecular formula	C22H25NO3
Molecular weight	351.4
InChIKey	MUTNCGKQJGXKEM-UHFFFAOYSA-N

SMILES: CC1(CCC(C2=C1C=CC(=C2)NC(=O)C3=CC=C(C=C3)C(=O)O)(C)C)C

IUPAC name: 4-[(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)carbamoyl]benzoic acid

ChEBI definition: A dicarboxylic acid monoamide resulting from the condensation of one of the carboxy groups of terephthalic acid with the amino group of 5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-amine.

Pharmacological roles (ChEBI): antineoplastic agent, retinoic acid receptor α/β agonist.

Also known as: AM-80, Amnoid, Am80, INNO-507, NSC-608000, OP-01, RR-110, Sy-1425, SY-1425, Tamibarotene, Tamibaroteno, TM-411

Patent coverage: 1,449 distinct patent families (5,139 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 4,570 (89%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
RARA	Retinoic acid receptor-α	Agonist	6.9	0.8%	P10276
RARB	Retinoic acid receptor-β	Agonist	6.63	0.1%	P10826
RARG	Retinoic acid receptor-γ	Agonist	6.23	1.6%	P13631

Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: Retinoic acid receptor gamma, Retinoic acid receptor beta, Retinoic acid receptor alpha, Thromboxane A2 receptor, Progesterone receptor, Menin/Histone-lysine N-methyltransferase MLL, Adenosine receptor A3, Cytochrome P450 3A4, Flavin reductase (NADPH), Cytochrome P450 26A1.

Bioactivity

ChEMBL activities: 12 potent at pChembl ≥ 5 of 18 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
RARA	8.19	Ki	6.5	nM	CHEMBL_ACT_636015
RARB	7.52	Ki	30	nM	CHEMBL_ACT_636016
RARA	7.35	EC50	45	nM	CHEMBL_ACT_3526118
RARA	7.3	EC50	50	nM	CHEMBL_ACT_26335883
RARA	7.11	IC50	78	nM	CHEMBL_ACT_496727
RARB	6.7	EC50	200	nM	CHEMBL_ACT_26335884
RARB	6.63	EC50	235	nM	CHEMBL_ACT_3526119
RARG	6.23	EC50	591	nM	CHEMBL_ACT_3526120
RARG	6.22	EC50	600	nM	CHEMBL_ACT_26335885
BLVRB	5.86	Kd	1380	nM	CHEMBL_ACT_24380451
BLVRB	5.86	Kd	1380	nM	CHEMBL_ACT_24380452
TBXA2R	5	AC50	9940	nM	CHEMBL_ACT_25197803

Target pathways

Aggregated over 3 target gene(s): RARA, RARB, RARG.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Nuclear Receptor transcription pathway	3	RARA, RARB, RARG
Signaling by Retinoic Acid	3	RARA, RARB, RARG
Activation of anterior HOX genes in hindbrain development during early embryogenesis	3	RARA, RARB, RARG
SUMOylation of intracellular receptors	1	RARA
Transcriptional regulation of granulopoiesis	1	RARA
TGFBR3 expression	1	RARA

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	3
glandular epithelial cell development	3
growth plate cartilage development	3
cell differentiation	3
regulation of myelination	3
multicellular organism growth	3
positive regulation of transcription by RNA polymerase II	3
retinoic acid receptor signaling pathway	3
negative regulation of cartilage development	3
regulation of DNA-templated transcription	3
bone development	3
ureteric bud development	2
neural tube closure	2
outflow tract septum morphogenesis	2
positive regulation of cell population proliferation	2

Indications & clinical

Indications

10 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
myelodysplastic syndrome	3	MONDO:0018881	EFO:0000198
Crohn disease	2	MONDO:0005011	EFO:0000384
acute myeloid leukemia	2	MONDO:0018874	EFO:0000222
acute promyelocytic leukemia	2	MONDO:0012883	EFO:0000224
lupus nephritis	2	MONDO:0005556	EFO:0005761
tropical spastic paraparesis	2	MONDO:0008039	EFO:0007527
Alzheimer disease	2	MONDO:0004975	MONDO:0004975
autosomal dominant polycystic kidney disease	2	MONDO:0004691	EFO:1001496
exocrine pancreatic carcinoma	1	MONDO:0005192	EFO:0002618
chronic myelomonocytic leukemia	1	MONDO:0020311	EFO:1001779

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE2	7
PHASE1/PHASE2	2
PHASE2/PHASE3	1
PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01343355	PHASE2/PHASE3	UNKNOWN	Efficacy and Safety of Tamibarotene(AM80H) for HTLV-1 Associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP)
NCT04797780	PHASE3	TERMINATED	Tamibarotene Plus Azacitidine in Participants With Newly Diagnosed RARA-positive Higher-Risk Myelodysplastic Syndrome
NCT06289998	PHASE2	ACTIVE_NOT_RECRUITING	Study of Tamibarotene in Patients With ADPKD
NCT00520208	PHASE2	COMPLETED	Safety, Efficacy, & Pharmacokinetic Study of Tamibarotene to Treat Patients With Relapsed or Refractory APL
NCT01120002	PHASE2	UNKNOWN	Efficacy and Safety of Tamibarotene (OAM80) for Alzheimer’s Disease
NCT01226147	PHASE2	UNKNOWN	Efficacy and Safety of Tamibarotene(AM80) for Lupus Nephritis
NCT01337154	PHASE2	TERMINATED	First Line Study of Tamibarotene in Combination for Advanced Non-Small Cell Lung Cancer
NCT02807558	PHASE2	COMPLETED	A Biomarker-Directed Phase 2 Trial of Tamibarotene (SY-1425) in Participants With Acute Myeloid Leukemia or Myelodysplastic Syndrome
NCT04905407	PHASE2	TERMINATED	Tamibarotene Plus Venetoclax/Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)
NCT05064618	PHASE1/PHASE2	UNKNOWN	Investigator-initiated Clinical Trial of MIKE-1
NCT06085638	PHASE1/PHASE2	WITHDRAWN	Phase I/II Study of SY-1425 (Tamibarotene) in Combination With Azacitidine and Venetoclax for Patients With Chronic Myelomonocytic Leukemia
NCT00985530	PHASE1	TERMINATED	Tamibarotene and Arsenic Trioxide for Relapsed Acute Promyelocytic Leukemia

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
PML K227_T233del	Acute Promyelocytic Leukemia	Resistance	Tamibarotene + Tretinoin	CIViC C	EID8175

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

42 molecules share ≥1 primary target. Top 42 by shared-target count:

Molecule	Source	Status	Shared targets
Acetaminophen	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
ADAPALENE	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
ALITRETINOIN	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Alprostadil	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Amoxicillin	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
BEXAROTENE	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
cyclosporine	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Olanzapine	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Rosiglitazone	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
TAZAROTENE	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Tolcapone	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
TRETINOIN	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
TRIFAROTENE	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
Zafirlukast	ChEMBL + PubChem	Phase 4 (approved)	RARA, RARB, RARG
CONESSINE	ChEMBL	Phase 2	RARA, RARB, RARG
GLIQUIDONE	ChEMBL	Phase 2	RARA, RARB, RARG
Atorvastatin	PubChem	Approved	RARA, RARB, RARG
Bosentan	PubChem	Approved	RARA, RARB, RARG
Calcitriol	PubChem	Approved	RARA, RARB, RARG
Carprofen	PubChem	Approved	RARA, RARB, RARG
Diclofenac	PubChem	Approved	RARA, RARB, RARG
ethinyl estradiol	PubChem	Approved	RARA, RARB, RARG
Repaglinide	PubChem	Approved	RARA, RARB, RARG
rifampin	PubChem	Approved	RARA, RARB, RARG
Simvastatin	PubChem	Approved	RARA, RARB, RARG
Sunitinib	PubChem	Approved	RARA, RARB, RARG
Ticlopidine	PubChem	Approved	RARA, RARB, RARG
Verapamil	PubChem	Approved	RARA, RARB, RARG
TROGLITAZONE	ChEMBL	Phase 4 (approved)	RARB, RARG
Rivaroxaban	PubChem	Approved	RARB, RARG
IBUPROFEN	ChEMBL	Phase 4 (approved)	RARB
KETOCONAZOLE	ChEMBL	Phase 4 (approved)	RARB
RACECADOTRIL	ChEMBL	Phase 4 (approved)	RARG
TROVAFLOXACIN	ChEMBL	Phase 4 (approved)	RARB
MOLIBRESIB	ChEMBL	Phase 2	RARA
NRX195183	ChEMBL	Phase 2	RARA
arsenic trichloride	PubChem	Approved	RARA
arsenic triiodide	PubChem	Approved	RARA
Domperidone	PubChem	Approved	RARG
Pitavastatin	PubChem	Approved	RARG
Retinol	PubChem	Approved	RARA